ABCC8 p.Leu1566Ala
| Predicted by SNAP2: | A: D (63%), C: N (61%), D: D (75%), E: D (75%), F: D (53%), G: D (71%), H: D (71%), I: N (82%), K: D (71%), M: N (87%), N: D (66%), P: D (75%), Q: D (63%), R: D (66%), S: D (63%), T: D (59%), V: N (57%), W: D (63%), Y: D (63%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] The C terminus of SUR1 is required for trafficking... J Biol Chem. 1999 Jul 16;274(29):20628-32. Sharma N, Crane A, Clement JP 4th, Gonzalez G, Babenko AP, Bryan J, Aguilar-Bryan L
The C terminus of SUR1 is required for trafficking of KATP channels.
J Biol Chem. 1999 Jul 16;274(29):20628-32., [PMID:10400694]
Abstract [show]
In beta cells from the pancreas, ATP-sensitive potassium channels, or KATP channels, are composed of two subunits, SUR1 and KIR6.2, assembled in a (SUR1/KIR6.2)4 stoichiometry. The correct stoichiometry of channels at the cell surface is tightly regulated by the presence of novel endoplasmic reticulum (ER) retention signals in SUR1 and KIR6.2; incompletely assembled KATP channels fail to exit the ER/cis-Golgi compartments. In addition to these retrograde signals, we show that the C terminus of SUR1 has an anterograde signal, composed in part of a dileucine motif and downstream phenylalanine, which is required for KATP channels to exit the ER/cis-Golgi compartments and transit to the cell surface. Deletion of as few as seven amino acids, including the phenylalanine, from SUR1 markedly reduces surface expression of KATP channels. Mutations leading to truncation of the C terminus of SUR1 are one cause of a severe, recessive form of persistent hyperinsulinemic hypoglycemia of infancy. We propose that the complete loss of beta cell KATP channel activity seen in this form of hyperinsulinism is a failure of KATP channels to traffic to the plasma membrane.
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No. Sentence Comment
17 The amino acid substitutions, V1578A, F1574A, L1567A, L1566A, and D1561A, were introduced by double-overlap polymerase chain reaction using overlapping mutagenic primers.
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ABCC8 p.Leu1566Ala 10400694:17:54
status: NEW